The overarching objective of this Project is to identify genetic variants that are associated, both as main effects and via interactions with exposure to environmental stressors, with incident cardiovascular events or coronary artery disease (CAD). To accomplish this goal, we will evaluate genes found associated in Projects 1 and 2 with CVD endophenotypes or in Project 3 with hypertension or type II diabetes (T2D), for associations with incident cardiovascular events and angiographically documented CAD in the CATHGEN sample of approximately 10,000 patients who have undergone cardiac catheterization at Duke since 2001. CATHGEN is a unique resource of biological samples collected at time of cardiac catheterization combined with a carefully adjudicated clinical database comprising angiographically-defined extent and anatomical distribution of coronary artery disease, extensive clinical data on CHD risk factors, and annual follow-up for evaluation of incident cardiovascular events. The CATHGEN investigators, under non-overlapping support from their NHLBI grant, will be evaluating a broad range of genes that are biologically plausible contributors to CHD pathogenesis and/or course or have been reported to be associated with CHD for associations with CAD and clinical events. Therefore, another aim of this Project, will be to collaborate with Projects 1, 2 and 3 to determine whether any genetic variants we fmd associated with CAD or clinical events in the CATHGEN sample are also associated with CVD endophenotypes, hypertension and/or T2D in their samples. As with Project 3, this Project provides the opportunity to take the critical step of translating gene associations with CVD endophenotypes into documented impact on disease endpoints.